The conserved C2 domain protein lethal (2) giant discs regulates protein trafficking in Drosophila
The conserved C2 domain protein lethal (2) giant discs regulates protein trafficking in Drosophila
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DOI：
10.1016/j.devcel.2006.09.014
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发表时间：
2006-11-01
影响因子：
11.8
通讯作者：
Knoblich, Juergen A.
中科院分区：
文献类型：
--
作者：
Gallagher, Ciara M.;Knoblich, Juergen A.
果蝇感觉器官前体（SOP）细胞经过几轮不对称的细胞分裂，产生组成外部感觉器官的四种不同类型的细胞。SOP子细胞间不同命运的建立依赖于Notch通路的差异调控。在这里，我们确定了致命(2)巨盘（Lgd）蛋白是SOP谱系中Notch信号的关键调节因子。我们发现lgd编码一个保守的C2结构域蛋白，该蛋白与早期核内体上存在的磷脂结合。当Lgd功能受损时，Notch和其他跨膜蛋白在扩大的早期内体区室中积聚。这些扩大的核内体对Rab5和Hrs呈阳性，这是一种参与运输到降解途径的蛋白质。我们的实验表明，Lgd是酵母中不存在的内吞作用的关键调节因子，并在Hrs后的降解途径中起作用。
Drosophila sensory organ precursor (SOP) cells undergo several rounds of asymmetric cell division to generate the four different cell types that make up external sensory organs. Establishment of different fates among daughter cells of the SOP relies on differential regulation of the Notch pathway. Here, we identify the protein Lethal (2) giant discs (Lgd) as a critical regulator of Notch signaling in the SOP lineage. We show that lgd encodes a conserved C2 domain protein that binds to phospholipids present on early endosomes. When Lgd function is compromised, Notch and other transmembrane proteins accumulate in enlarged early endosomal compartments. These enlarged endosomes are positive for Rab5 and Hrs, a protein involved in trafficking into the degradative pathway. Our experiments suggest that Lgd is a critical regulator of endocytosis that is not present in yeast and acts in the degradative pathway after Hrs.